An examination of the psychologists' attitudes towards complementary and alternative therapies scale within a practitioner sample

This study assessed the validity of a scale measuring psychologists' attitudes towards complementary and alternative therapies and compared the attitudes of psychologists with a previous sample of psychology students. The scale, derived from existing measures for medical professionals and previously tested on a sample of psychology students, was completed by practising psychologists (N = 122). The data were factor analysed, and three correlated subscales were identified, assessing the perceived importance of knowledge about available therapies, attitudes towards integration with psychological practice, and concerns about associated risks of use. This structure was similar, but not identical, to that found in a previous sample of psychology students; however, psychologists expressed more concern for risks associated with integration and were less likely to hold a positive attitude towards integration. This scale will be useful in gauging changes in psychologists' attitudes towards integrative practice over time.

PARP inhibition induces BAX/BAK-independent synthetic lethality of BRCA1-deficient non-small cell lung cancer

Evasion of apoptosis contributes to both tumourigenesis and drug resistance in non-small cell lung carcinoma (NSCLC). The pro-apoptotic BCL-2 family proteins BAX and BAK are critical regulators of mitochondrial apoptosis. New strategies for targeting NSCLC in a mitochondria-independent manner should bypass this common mechanism of apoptosis block. BRCA1 mutation frequency in lung cancer is low; however, decreased BRCA1 mRNA and protein expression levels have been reported in a significant proportion of lung adenocarcinomas. BRCA1 mutation/deficiency confers a defect in homologous recombination DNA repair that has been exploited by synthetic lethality through inhibition of PARP (PARPi) in breast and ovarian cells; however, it is not known whether this same synthetic lethal mechanism exists in NSCLC cells. Additionally, it is unknown whether the mitochondrial apoptotic pathway is required for BRCA1/PARPi-mediated synthetic lethality. Here we demonstrate that silencing of BRCA1 expression by RNA interference sensitizes NSCLC cells to PARP inhibition. Importantly, this sensitivity was not attenuated in cells harbouring mitochondrial apoptosis block induced by co-depletion of BAX and BAK. Furthermore, we demonstrate that BRCA1 inhibition cannot override platinum resistance, which is often mediated by loss of mitochondrial apoptosis signalling, but can still sensitize to PARP inhibition. Finally we demonstrate the existence of a BRCA1-deficient subgroup (11–19%) of NSCLC patients by analysing BRCA1 protein levels using immunohistochemistry in two independent primary NSCLC cohorts. Taken together, the existence of BRCA1-immunodeficient NSCLC suggests that this molecular subgroup could be effectively targeted by PARP inhibitors in the clinic and that PARP inhibitors could be used for the treatment of BRCA1-immunodeficient, platinum-resistant tumours.

Behavioural changes add validity to the construct of posttraumatic growth

The research aimed to identify positive behavioural changes that people may make as a result of negotiating the aftermath of a traumatic experience, thereby extending the current cognitive model of posttraumatic growth (PTG). It was hypothesised that significant others would corroborate survivor’s cognitive and behavioural reports of PTG. The sample comprised 176 participants; 88 trauma survivors and 88 significant others. University students accounted for 64% of the sample and 36% were from the broader community. Approximately one third were male. All participants completed the Posttraumatic Growth Inventory [PTGI] and open ended questions regarding behavioural changes. PTGI scores in the survivor sample were corroborated by the significant others with only the Appreciation of Life factor of the PTGI differing between the two groups (e.g., total PTGI scores between groups explained 33.64% of variance). Nearly all of the survivors also reported positive changes in their behaviour and these changes were also corroborated by the significant others. Results provide validation of the posttraumatic growth construct and the PTGI as an instrument of measurement. Findings may also influence therapeutic practice for example, the potential usefulness of corroborating others.

A general method to determine sampling windows for nonlinear mixed effects models with an application to population pharmacokinetic studies

Optimal design methods have been proposed to determine the best sampling times when sparse blood sampling is required in clinical pharmacokinetic studies. However, the optimal blood sampling time points may not be feasible in clinical practice. Sampling windows, a time interval for blood sample collection, have been proposed to provide flexibility in blood sampling times while preserving efficient parameter estimation. Because of the complexity of the population pharmacokinetic models, which are generally nonlinear mixed effects models, there is no analytical solution available to determine sampling windows. We propose a method for determination of sampling windows based on MCMC sampling techniques. The proposed method attains a stationary distribution rapidly and provides time-sensitive windows around the optimal design points. The proposed method is applicable to determine sampling windows for any nonlinear mixed effects model although our work focuses on an application to population pharmacokinetic models.